Platanic acid derived amides are more cytotoxic than their corresponding oximes

Abstract

Albeit platanic acid has been known since 1956, its potential to act as a valuable starting material for the synthesis of cytotoxic agents has been neglected for many years. Hereby we describe the synthesis of a small library of amides and oximes derived from 3-O-acetyl-platanic acid, and the results of their screening as cytotoxic agents for several human tumor cell lines. As a result, while the cytotoxicity of the oximes was diminished as compared to the parent amides, the homopiperazinyl amide 5 held the highest cytoxicity (EC50 = 0.9 μM for A375 human melanoma cells). Extra FACS and cell cycle measurements showed compound 5 to act onto A375 cells rather by apoptosis than by necrosis. Clinical trial registration No clinical trials are associated with this study

Betulonic and Platanic Acids as a Basis for the Synthesis of New Therapeutically Effective Substances

“…Kozubek a spol. 15 zjistili, že cytotoxická aktivita amidů platanové kyseliny je vyšší než u odpovídajících oximů. Amidy v pozici C-28 odvozené od ethylaminu, morfolinu či homopiperazinu vykazovaly vysokou cytotoxicitu na všechny typy lidských nádorových buněk, ale také na linii nemaligních myších fibroblastů a lidských embryonálních ledvinových buněk 15 .…”

Oxime derivatives of betulonic acid and platanic acid as novel cytotoxic or antiviral agents

“…27,28 We have reviewed platanic acid, besides other triterpenoids, and its selected nitrogen-group-bearing derivatives recently. 3 Nevertheless, before the review paper has been published, several new papers have appeared in the literature: pentacyclic triterpenoid sulphamates used for radiotherapy of breast cancer, 29 nitrogen-group-bearing bicyclic compounds used as inhibitors of butyrylcholinesterase, 30,31 pyridinylidene derivatives developed for targeting apoptosis, 32 platanic acid amides 33,34 and even more complex derivatives of platanic acid 35 for investigating cytotoxicity.…”

The Finally Rewarding Search for A Cytotoxic Isosteviol Derivative

“…Since previous work also indicated an effect on mitochondrial permeability transition [ 35 ], it was natural to transfer our own previous findings on pentacyclic triterpenes to the diterpene isosteviol. Of particular interest were benzyl and pyridine-amides, (iso)-quinoline amides, and especially (homo)-piperazinyl-spacered rhodamine B and rhodamine 101 conjugates [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”